The cumulative risk of false-positive screening results across screening centres in the Norwegian Breast Cancer Screening Program.

BACKGROUND: Recall for assessment in mammographic screening entails an inevitable number of false-positive screening results. This study aimed to investigate the variation in the cumulative risk of a false positive screening result and the positive predictive value across the screening centres in the Norwegian Breast Cancer Screening Program. METHODS: We studied 618,636 women aged 50-69 years who underwent 2,090,575 screening exams (1996-2010. Recall rate, positive predictive value, rate of screen-detected cancer, and the cumulative risk of a false positive screening result, without and with invasive procedures across the screening centres were calculated. Generalized linear models were used to estimate the probability of a false positive screening result and to compute the cumulative false-positive risk for up to ten biennial screening examinations. RESULTS: The cumulative risk of a false-positive screening exam varied from 10.7% (95% CI: 9.4-12.0%) to 41.5% (95% CI: 34.1-48.9%) across screening centres, with a highest to lowest ratio of 3.9 (95% CI: 3.7-4.0). The highest to lowest ratio for the cumulative risk of undergoing an invasive procedure with a benign outcome was 4.3 (95% CI: 4.0-4.6). The positive predictive value of recall varied between 12.0% (95% CI: 11.0-12.9%) and 19.9% (95% CI: 18.3-21.5%), with a highest to lowest ratio of 1.7 (95% CI: 1.5-1.9). CONCLUSIONS: A substantial variation in the performance measures across the screening centres in the Norwegian Breast Cancer Screening Program was identified, despite of similar administration, procedures, and quality assurance requirements. Differences in the readers' performance is probably of influence for the variability. This results underscore the importance of continuous surveillance of the screening centres and the radiologists in order to sustain and improve the performance and effectiveness of screening programs.

Stage distribution of breast cancer diagnosed before and after implementation of population-based mammographic screening.

PURPOSE: The German mammographic screening program is very similar to the Norwegian Breast Cancer Screening Program (NBCSP), which started about 10 years earlier. This study analyzes the stage distribution of invasive breast cancers diagnosed in the pre-screening and screening period, and evaluates the overall mortality in women aged 55-74 in the pilot and non-pilot counties of the NBCSP. MATERIALS AND METHODS: The NBCSP invites women aged 50-69 to participate in two-view mammography biennially. Chi-square statistics were used to compare percentages of the stage and treatment of invasive breast cancers diagnosed in women residing in the four pilot counties in the pre-screening (1984-1995) and screening (1996-2007) period. An ecological approach was used to analyze the age-specific mortality in the pilot and non-pilot counties for the period 1970-2007. RESULTS: 50% of the breast cancers diagnosed in the pre-screening period, 70% of the cases detected with screening, 43% of the interval cancers, and 52% of the cancers diagnosed outside the NBCSP were stage I. Stage III+was present in 11% of the cancers in the pre-screening period, and in 1% of the cancers detected with screening. In the screening period, the breast cancer mortality rate decreased substantially more in the pilot counties than in the non-pilot counties. CONCLUSION: The stage distribution of breast cancer diagnosed in the NBCSP is prognostically favorable compared to cancers diagnosed outside the screening program. The reduction in the breast cancer mortality rate was more pronounced in the four pilot counties compared to the non-pilot counties. It is necessary to evaluate the program based on individual data.

Studies comparing screen-film mammography and full-field digital mammography in breast cancer screening: updated review.

Full-field digital mammography (FFDM) has several potential benefits as compared with screen-film mammography (SFM) in mammography screening. Digital technology also opens for implementation of advanced applications, including computer-aided detection (CAD) and tomosynthesis. Phantom studies and experimental clinical studies have shown that FFDM is equal or slightly superior to SFM for detection and characterization of mammographic abnormalities. Despite obvious advantages, the conversion to digital mammography has been slower than anticipated, and not only due to higher costs. Until very recently, some countries did not even permit the use of digital mammography in breast cancer screening. The reason for this reluctant attitude was concern about lower spatial resolution and about using soft-copy reading. Furthermore, there was a lack of data supporting improved diagnostic accuracy using FFDM in a screening setting, since two pioneer trials both showed nonsignificantly lower cancer detection rate at FFDM. The 10 studies comparing FFDM and SFM in mammography screening published so far have shown divergent and rather conflicting results. Nevertheless, there is a rapid conversion to digital mammography in breast cancer screening in many western countries. The aim of this article is to give an updated review of these studies, discuss the conflicting findings, and draw some conclusions from the results.

Mammographic features and histopathological findings of interval breast cancers.

BACKGROUND: Interval cancers are considered a shortcoming in screening mammography due to less favorable prognostic tumor characteristics compared to screening-detected cancers and consequently a lower chance of survival from the disease. PURPOSE: To describe the mammographic features and prognostic histopathological tumor characteristics of interval breast cancers. MATERIAL AND METHODS: A total of 231 interval breast cancer cases diagnosed in prevalently screened women aged 50-69 years old were examined. Thirty-five percent of the cases were retrospectively classified as missed cancers, 23% as minimal sign, and 42% as true negative (including occult cancers) in a definitive classification performed by six experienced breast radiologists. The retrospective classification described the mammographic features of the baseline screening mammograms in missed and minimal-sign interval cancers, while histopathological reports were used to describe the tumor characteristics in all the subgroups of interval cancers. RESULTS: Fifty percent of the missed and minimal-sign interval cancers combined presented poorly defined mass or asymmetric density, and 26% calcifications with or without associated density or mass at baseline screening. Twenty-seven percent of invasive tumors were <15 mm for missed and 47% for true interval cancers (P<0.001). Lymph node involvement was more common in missed (49%) compared with the true cases (33%, P<0.05). CONCLUSION: Missed interval cancers have less prognostically favorable histopathological tumor characteristics compared with true interval cancers. Improving the radiologist's perception and interpretation by establishing systematic collection of features and implementation of organized reviews may decrease the number of interval cancers in a screening program.

Differential impact of conventional and low-dose oral hormone therapy, tibolone and raloxifene on mammographic breast density, assessed by an automated quantitative method.

OBJECTIVE: To evaluate impact of different postmenopausal hormone therapy (HT) regimens and raloxifene on mammographic breast density. DESIGN: Open, randomised, comparative clinical trial. SETTING: Women were recruited through local newspapers and posters. They were examined at the Departments of Haematology, Gynaecology, and Radiology in a University Hospital. POPULATION: A total of 202 healthy postmenopausal women between the age of 45 and 65 years. METHODS: Women were randomly assigned to receive daily treatment for 12 weeks with tablets containing low-dose HT containing 1 mg 17 beta-estradiol + 0.5 mg norethisterone acetate (NETA) (n = 50), conventional-dose HT containing 2 mg 17 beta-estradiol and 1 mg NETA (n = 50), 2.5 mg tibolone (n = 51), or 60 mg raloxifene (n = 51). Mammographic density was determined at baseline and after 12 weeks by an automated technique in full-field digital mammograms. MAIN OUTCOME MEASURES: Mammographic density was expressed as volumetric breast density estimations. RESULTS: Mammographic breast density increased significantly and to a similar degree in both the conventional- and low-dose HT groups. A small reduction in mammographic breast density was seen in the raloxifene group, whereas those allocated to tibolone treatment only showed minor changes. CONCLUSIONS: Our findings demonstrated a significant difference in impact on mammographic breast density between the regimens. Although these results indicate a differential effect of these regimens on breast tissue, the relation to breast cancer risk remains unresolved.

Reduction in dose from CT examinations of liver lesions with a new postprocessing filter: a ROC phantom study.

BACKGROUND: It is desirable to lower the dose from computed tomography (CT) examinations as much as possible without reducing diagnostic performance. Mathematical postprocessing filters are one tool to achieve dose reduction. PURPOSE: To evaluate the possibilities of reducing CT doses from liver examinations using a new postprocessing filter. MATERIAL AND METHODS: An anthropomorphic upper-abdomen phantom was used in receiver operating characteristic (ROC) studies of the detectability of liver lesions. A standard abdominal CT protocol was used. Only mA settings were changed; all other scan parameters were constant. The postprocessing filter used was SharpView CT, which provides context-controlled restoration of digital images using adaptive filters. Six readers were given a set of 10 images obtained at five different dose levels, each image with 32 predefined areas to be evaluated on a five-point scale. In total, 1920 areas were evaluated. At each dose level, the readers evaluated five images without enhancement and five images based on postprocessing filters. All images were randomized with respect to dose level. RESULTS: The postprocessing filter improved the diagnostic performance significantly compared to the unenhanced images at all dose levels. Radiation dose for abdominal CT examinations of liver lesions in the range 2-7 mm was reduced by 30% using postprocessing filters, while diagnostic performance of the examination was maintained or even improved. CONCLUSION: This study indicates great potential for lowering doses for CT examinations of liver lesions using the new postprocessing filter. The software must be fully tested clinically to reliably assess the benefits of this filtration.

Follow-up and final results of the Oslo I Study comparing screen-film mammography and full-field digital mammography with soft-copy reading.

PURPOSE: To compare cancer detection rates of screen-film (SFM) and full-field digital mammography (FFDM) with soft-copy reading in a screening program including the initial positive scores for interval cancers and cancers in the subsequent screening round, and to analyze the false-negative FFDM interpretations. MATERIAL AND METHODS: Using a paired study design, 3683 women underwent SFM and FFDM in a population-based screening program. Two standard views of each breast were acquired. The images were interpreted without previous films for comparison. Independent double reading using a 5-point rating scale for probability of cancer was used for each modality. An examination was defined as positive if at least one of the two independent readers scored 2 or higher on the 5-point rating scale. SFM-positive cases were discussed in a SFM consensus meeting and FFDM-positive cases in a separate FFDM consensus meeting before recall. The study population was followed for more than 2 years so that interval cancers and screen-detected cancers in the subsequent screening round could be included. Cancer detection rates were compared using the McNemar test for paired proportions. The kappa statistic and Wilcoxon signed-rank test for matched pairs were used for comparing rating scores. The reading time was recorded for all FFDM interpretations. RESULTS: A total of 31 cancers (detection rate 0.84%) were diagnosed initially, of which SFM detected 28 and FFDM 23 (McNemar test P=0.23, discordant pair 8 and 3). Two cancers with a positive score at initial SFM reading and three with a positive score at initial FFDM reading were dismissed at SFM and FFDM consensus meetings, respectively. The difference in cancer detection after recall (discordant pair 11 and 5) was not significant (McNemar test, P=0.21). Of the 10 interval cancers and 16 screen-detected cancers in the subsequent round, 3 had true-positive SFM scores while 4 had true-positive FFDM scores in the initial reading session. A total of 38 cancers therefore had a positive result at double reading at one or both modalities, 31 at SFM and 27 at FFDM (McNemar test, P=0.48). Comparison of SFM and FFDM interpretations using the mean score for each case revealed no statistically significant difference between the two modalities (Wilcoxon signed-rank test for matched pairs; P-value=0.228). Two initial round cancers (one tumor found incidentally at work-up for a mass proved to be a simple cyst with a positive score at FFDM but a negative score at SFM, and one tumor with positive score at SFM but negative score at FFDM due to positioning failure) were excluded from the further analysis. Excluding these two cancers from comparison, there were 31% (22 of 72) false-negative SFM and 47% (34 of 72) false-negative FFDM individual interpretations. The overall mean interpretation time for normal FFDM examinations was 45 s. For most false-negative FFDM results, the reading time was shorter or longer than for normal examinations. The recorded FFDM interpretation time was noticeably short for several overlooked cancers manifesting as microcalcifications (ductal carcinoma in situ). CONCLUSION: There is no statistically significant difference in cancer detection rate between SFM and FFDM with soft-copy reading in a mammography screening program. Analysis of cancers missed at FFDM with soft-copy reading indicates that close attention has to be paid to systematic use of image display protocols.

Migration of the breast biopsy localization wire to the pulmonary hilus.

There have been very few reports of severe complications accompanied by wire localization of breast lesions, such as transsection of the wire and wire migration to the extramammary sites. This is a report of wire migration into the pulmonary hilus demanding surgical removal.

Logistics of referral, diagnostic assessment and treatment of patients with breast symptoms and signs.

BACKGROUND AND AIMS: The logistics of diagnosis and treatment in a hospital with slightly above 400 new cases of breast cancer per year is analysed. MATERIALS AND METHODS: The patient flow from referral, through the diagnostic procedures and through surgical treatment is described. RESULTS AND CONCLUSIONS: The basic principle of the diagnostic assessment is the triple diagnostic procedure including mammography supplemented by ultrasonography, fine needle aspiration cytology and clinical examination. The radiologist and pathologist are working together in the breast diagnostic centre and are thus able to give a "single visit diagnosis" in most cases. The surgeon sees the patient either the same day or the next. A "consensus meeting" held each week with representatives for all specialities present has an important function in quality assurance and education. If one or more of the triple diagnostic components reach conclusion level "suspicious lesion", surgery is indicated. In hospital management is based on day surgery for all biopsies, wide excisions with or without sentinel node and some ablatio simplex mammae. For wide excision and ablation with complete axillary node clearance, the patients are transferred from the day surgery unit to a patient hotel after 3-4 hours of observation and stay till the drain can be removed. Only in rare case of high cardiopulmonary risk, beds in ordinary wards are used. This is a highly cost efficient logistic saving the hospital approximately 400,000 EUR a year compared to ordinary in hospital treatment.

Interval cancers in the Norwegian breast cancer screening program: frequency, characteristics and use of HRT.

Breast cancers diagnosed between screening examinations among women who attend a breast cancer screening program are defined as interval cancers. The Norwegian Breast Cancer Screening Program started as a pilot project in 1996, and data from the first 2-year interval are available. Our study quantifies interval cancers in the pilot project and explores characteristics and factors that may be associated with interval cancer. Interval cancers in the screening population were identified through the Cancer Registry of Norway. The frequency of invasive interval cancer was calculated as cases per 10,000 screened and as observed/expected ratio. Characteristics of the interval cancers were compared to screening-detected and clinical cancers. Breast density was assessed in a blinded review of 3 categories of screening mammograms. Information on hormone replacement therapy (HRT) use was collected from a questionnaire. The frequency of invasive interval cancers was 18.2 (15.9-20.7) per 10,000 screened and the observed/expected ratio was 0.49 (0.43-0.56). The frequency in the second year of the interval was higher than reported from other programs. The median tumor size of the interval cancers was 19.5 mm and 44.0% of the patients had affected axillary lymph nodes. The interval cancer cases had higher proportions of dense breasts and reported use of HRT compared to screen normal and screening-detected cases. The reported frequency of interval cancers is similar to comparable programs. The interval cancers differed significantly from the cancers detected in the first screening round and were more similar to clinical cancers. Interval cancer was associated with dense breasts and use of HRT. Screening programs must keep these associations in focus.

[Diagnostic and therapeutic localized breast biopsy]. / Diagnostisk og terapeutisk merkebiopsi i mammae.

Preoperative localized mammary biopsy has been used as a diagnostic tool since before 1983 in the Breast Clinic, Ullevål Hospital. The great majority of procedures have been performed in the outpatient clinic with use of local anesthesia. Since 1988 all activity has been registered prospectively in a database. We discuss the use of the procedure and the results obtained during the period 1983-95. In the later part of the observed period, the use of the procedure as a diagnostic tool has been less frequent, but it has been increasingly used as a tool to identify the pathologic process when performing breast-conserving surgery. Surveillance of the malign-benign ratio is an important parameter in the quality assurance of the procedure. The malign-benign ratio has been greater than 0.3 during the period of observation. Continuous registration of procedure-related parameters is necessary for documentation of the results.

[A prospective registration of diagnosis and treatment of breast tumors at the Ulleval hospital 1988-1995]. / En prospektiv registrering av diagnostikk og behandling av tumor mammae ved Ullevål sykehus 1988-95.

During the years 1988 to 1995, all diagnostic and therapeutic activities in the Breast Clinic, Ullevål Hospital, Oslo, Norway were registered prospectively. This paper presents the results from the registration. Of 4,436 new referrals, 1,169 had infiltrating mammary carcinoma and 63 ductal carcinoma in situ. 13.6% of those with breast carcinoma and 12.3% of those with benign breast disease had a first degree relative with breast cancer. The use of diagnostic biopsies for palpable and nonpalpable lesions decreased significantly through the period, from 155/112 in 1988 to 65/78 in 1995. For palpable lesions, the malign/benign ratio decreased from 0.82 in 1988 to 0.54 in 1995 while it improved from 0.43 to 0.88 for marked biopsies for nonpalpable lesions. Excluding those with mammographically and/or cytologically suspicious lesions from those who had a biopsy for a palpable lesion, we found that only seven out of 101 had cancer (ratio 0.07). Radical surgery was done in 790 cases with cytology as the only pre- and peroperative cancer verification. Three of them had a false positive cytology, as cancer was not found in the breast. One patient had metastasis later confirming that a cancer had been present; thus we had two false positive cytologies (2.5 per thousand). More than six axillary lymph nodes have to be examined in order to avoid false negative axillary status. In 1988 we had 41% with less than six nodes examined. This improved to 15% in 1995. Breast preserving therapy increased throughout the period from 4.1% in 1988 to 29.4% in 1995. Tumor size (pTI around 40%) and node positivity (35%) was fairly constant. In our opinion, a continuous prospective registration of the activity in a breast diagnostic centre is essential in order to improve and maintain service quality. The decision made by the Norwegian parliament in 1998 to introduce nation-wide mammography screening may be used to institute such continuous prospective registrations in all centres involved in the screening.

The additional value of US to mammography in the diagnosis of breast cancer. A prospective study.

PURPOSE: To assess the additional value of ultrasonography (US) to mammography in the diagnosis of malignant breast tumors. MATERIAL AND METHODS: Prospectively recorded final assessment categories for mammography and US were compared for 327 (228 palpable and 99 nonpalpable) consecutive malignant tumors confirmed at histology. The additional value of US was assessed for a subpopulation of 71 of these 327 malignancies after excluding mammographically conclusive malignant findings, ductal carcinomas in situ (DCIS), and invasive carcinomas presenting with suspicious microcalcifications, since there is no indication for performing US in these patients. RESULTS: A total of 267 (82%) of the 327 malignant tumors were correctly diagnosed on both imaging modalities. Mammography correctly diagnosed 41 cancers with false-negative US findings as compared with 11 true-positive US diagnoses of malignant tumors with false-negative findings on mammography (McNemar test p<0.001). US correctly diagnosed ("upgraded") 31 (10%) of the 327 malignant tumors with benign or indeterminate mammographic diagnoses. In the subpopulation, US upgraded 20 (42%) of 48 palpable and 10 (44%) of 23 nonpalpable malignant tumors. CONCLUSION: The overall additional value of US to mammography in the diagnosis of breast cancer was rather limited in a population of mixed malignant tumors. Excluding cancers with mammographically conclusive diagnosis and suspicious microcalcifications as well as DCIS from analysis, US correctly upgraded more than 40% of palpable and nonpalpable malignant tumors.

Ultrasonographic evaluation of invasive lobular carcinoma.

PURPOSE: To compare ultrasonographic (US) and mammographic findings and tumor size measurements of invasive lobular carcinoma (ILC). MATERIAL AND METHODS: US diagnoses and mammographic findings were compared in 95 patients with pure ILC, including 46 palpable and 49 nonpalpable tumors. The diameters of tumors measured by mammography, US, and pathology were compared in 70 of the 95 patients using scatter plots and correlation analysis. RESULTS: Eighty-two (86.3%) of the ILCs were correctly diagnosed as malignant tumor, 5 (5.3%) were diagnosed as focal abnormality, and only 2 patients had normal findings on US. The most common mammographic findings were a spiculated mass (57%) and a focal asymmetric density (15%). US correctly diagnosed 8 of 12 patients with normal or equivocal mammographic findings. The correlation of tumor size assessment on imaging and pathology revealed that US measurements including the "halo" (r=0.69) was superior to that of mammography (r=0.59). ILCs larger than 30 mm were heavily underestimated by both methods. CONCLUSION: Malignant tumor was diagnosed on US in most of the patients with ILC. US tumor measurement including the "halo" predicted tumor size most accurately. The correlation between imaging measurements and tumor diameter on histology was lower for ILCs than reported for populations of mixed carcinomas.

Ultrasonography of malignant breast neoplasms. Analysis of carcinomas missed as tumor.

PURPOSE: To analyze the malignant breast neoplasms missed as tumor on ultrasonography (US). MATERIAL AND METHODS: A total of 355 malignant tumors were confirmed at histology among 2,985 consecutive patients who underwent breast US. There were no prospectively recorded mammographic findings in 28 of the 355 tumors. The remaining 327 tumors included 16 ductal carcinomas in situ (DCIS) and 66 invasive carcinomas with suspicious microcalcifications on mammography. Excluding these 82 tumors because US would not have been indicated using strict criteria, a subpopulation of 245 noncalcified invasive malignant tumors remained for analysis. The neoplasms missed as tumor on US were analyzed for the whole tumor group (n=355) and the subpopulation (n=245). RESULTS: 42 (11.8%) of the 355 malignant neoplasms were missed as tumor on US, including 6 (2.5%) of the 243 palpable and 36 (32.1%) of the 1 12 nonpalpable malignancies. Most of the missed tumors were DCIS and microinvasive ductal carcinomas dominated by DCIS. In the subpopulation, 14 (5.7%) of the 245 malignancies were missed as tumor on US, including 4 (2.2%) of the 180 palpable and 10 (15.4%) of the 65 nonpalpable lesions. Of the 245 malignancies, 6 (2.4%) had a normal US finding, including 2 palpable retropapillary tumors and 4 incidental findings at histology. CONCLUSION: Using strict criteria for performing US as an adjunct to mammography, by far the most malignant breast neoplasms are diagnosed as a tumor on US.

Diagnostic value of ultrasonography in patients with palpable mammographically noncalcified breast tumors.

PURPOSE: To analyze the diagnostic accuracy of mammography, ultrasonography (US), and both methods combined in evaluation of palpable noncalcified breast tumors. MATERIAL AND METHODS: Mammograms and sonograms of 200 patients with palpable noncalcified breast masses were retrospectively analyzed independently by four experienced radiologists in 3 sessions: Mammography or US interpretations in the first two and combined reading in the last session. Nonneoplastic abnormalities and mammographically obvious cancers were excluded. Receiver operating characteristic (ROC) analyses were performed for 115 (60 benign and 55 malignant) tumors and subgroups according to tissue density and tumor size. A single ROC curve for each diagnostic test was obtained by pooling the individual ratings. The area under the ROC curve was used as a measure of diagnostic performance. RESULTS: US revealed significantly higher diagnostic performance than mammography for tumors larger than 2 cm. Combined reading showed significantly higher performance than mammography except for tumors smaller than 2 cm. The performance of all three tests was reduced in dense parenchyma, and significantly so for mammographic and combined interpretation. CONCLUSION: The accuracy of US in patients with palpable mammographically noncalcified and not obviously malignant breast tumors is lower than reported for mixed sample populations. The accuracy of US may be influenced by breast parenchyma density. Combined reading offers the highest diagnostic accuracy.

Variability in the interpretation of ultrasonography in patients with palpable noncalcified breast tumors.

PURPOSE: To analyze interobserver variability of ultrasonography (US) as an adjunct to mammography in patients with palpable noncalcified breast tumors. MATERIAL AND METHODS: Mammographic, US, and combined reading of 200 patients with palpable noncalcified breast masses were performed independently by four experienced radiologists. Nonneoplastic abnormalities and mammographically obvious cancers were excluded. Receiver operating characteristic (ROC) analysis based on 115 tumors was carried out for mammography, US, and both combined for each radiologist. The US diagnoses of the 45 cancers excluded from ROC analysis and the 55 cancers included were compared. RESULTS: One radiologist revealed a significantly higher diagnostic performance with US than with mammography. Combined reading showed the highest performance for all observers, but the improvement as compared with mammography was significant for only two. Higher accuracy on combined reading was mainly caused by correct upgrading of tumors with benign or indeterminate mammographic findings. One radiologist had benefit of US for downgrading of tumors. All four radiologists made a malignant US diagnosis twice as often in mammographically obvious cancers than in mammographically nonconclusive tumors. CONCLUSION: Radiologists differ substantially in interpretation of breast imaging. Combined reading offers the highest diagnostic accuracy mainly by correct upgrading of tumors on US. The role of US for downgrading tumors is operator-dependent.

Ultrasonography as adjunct to mammography in the evaluation of breast tumors.

PURPOSE: The aims of the study was to analyze the features of cancers missed as tumor on ultrasonography (US), to determine the predictive power of US tumor descriptors in the differentiation of benign and malignant breast tumors, to evaluate US as adjunct to mammography, and to assess the validity and reliability of mammographic, US, and combined interpretation of breast tumors. MATERIAL AND METHODS: Prospectively recorded mammographic and US findings of 355 malignant breast tumors among 2,985 consecutive patients who underwent breast US were compared with clinical findings and pathologic subtypes of the tumors. In addition, a 10-year material of 95 invasive lobular carcinomas (ILCs) were investigated. Three retrospective studies assessed the validity and reliability of mammographic, US, and combined interpretation of 200 palpable mammographically noncalcified breast masses by four radiologists. RESULTS: A total of 97.5% of the palpable and 67.9% of the nonpalpable malignant neoplasms were detected as tumor on US. Most carcinomas missed as tumor on US were ductal carcinomas in situ (DCISs) and microinvasive ductal cancers dominated by DCIS manifesting with suspicious calcifications on mammography. Irregular shape, irregular contour, extensively hypoechogenicity, hyperechoic rim (halo), and distortion of the surrounding tissue were the US features with the highest odds of predicting carcinomas. A pseudocapsule is the strongest predictor of a benign tumor, the odds of cancer being 0.03 in nonpalpable and 0.08 in palpable breast tumors. A negative predictive value of 100% in palpable and 96% in nonpalpable tumors was achieved using strict US criteria. In patients with ILC, US measurements predicted tumor size more accurately than mammography. US as adjunct to mammography correctly diagnosed ("upgraded") 9.5% of tumors with benign or indeterminate mammographic diagnoses. Excluding mammographically conclusive malignant tumors and carcinomas presenting with microcalcifications. US correctly upgraded 42% of the palpable and 44% of the nonpalpable cancers. Combined mammographic-US interpretation offers the highest diagnostic performance in noncalcified breast tumors. The lowest interobserver agreement was found in US interpretation. CONCLUSION: The impact of US in mixed cancer populations is limited. US is, however, a valuable adjunct to mammography in patients with nonconclusive mammographic findings. Negative predictive values on US approaching 100% may be achieved using strict criteria for a benign diagnosis. A considerable interobserver variation in the US interpretation is a limiting factor for the potential of breast US in the differentiation of benign and malignant breast tumors.